Variant 18-48942576-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005904.4(SMAD7):c.668-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,612,284 control chromosomes in the GnomAD database, including 25,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1706 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23417 hom. )

Consequence

SMAD7
NM_005904.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

SMAD7 (HGNC:6773): (SMAD family member 7) The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

SMAD7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 18-48942576-G-A is Benign according to our data. Variant chr18-48942576-G-A is described in ClinVar as [Benign]. Clinvar id is 3059472.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAD7	NM_005904.4 linkuse as main transcript	c.668-21C>T		intron_variant		ENST00000262158.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAD7	ENST00000262158.8 linkuse as main transcript	c.668-21C>T		intron_variant		1	NM_005904.4	P4	O15105-1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20487

AN:

152150

Hom.:

1706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.0786

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.143

AC:

35737

AN:

249634

Hom.:

3095

AF XY:

0.145

AC XY:

19627

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.0379

Gnomad AMR exome

AF:

0.0928

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.0602

Gnomad SAS exome

AF:

0.0781

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.173

AC:

252653

AN:

1460016

Hom.:

23417

Cov.:

AF XY:

0.172

AC XY:

124785

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.0355

Gnomad4 AMR exome

AF:

0.0981

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.0477

Gnomad4 SAS exome

AF:

0.0823

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.135

AC:

20484

AN:

152268

Hom.:

1706

Cov.:

AF XY:

0.133

AC XY:

9887

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.0650

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.182

Hom.:

2610

Bravo

AF:

0.129

Asia WGS

AF:

0.0780

AC:

272

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SMAD7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over